Abstract:
:Hepatocyte membranes from both lean and obese Zucker rats exhibited adenylate cyclase activity that could be stimulated by glucagon, forskolin, NaF and elevated concentrations of p[NH]ppG. In membranes from lean animals, functional Gi was detected by the ability of low concentrations of p[NH]ppG to inhibit forskolin-activated adenylate cyclase. This activity was abolished by treatment of hepatocytes with either pertussis toxin or the phorbol ester TPA, prior to making membranes for assay of adenylate cyclase activity. In hepatocyte membranes from obese animals no functional Gi activity was detected. Quantitative immunoblotting, using an antibody able to detect the alpha subunit of Gi, showed that hepatocyte plasma membranes from both lean and obese Zucker rats had similar amounts of Gi-alpha subunit. This was 6.2 pmol/mg plasma membrane for lean and 6.5 pmol/mg plasma membrane for obese animals. Using thiol pre-activated pertussis toxin and [32P]-NAD+, similar degrees of labelling of the 40 kDa alpha subunit of Gi were found using plasma membranes of both lean and obese Zucker rats. We suggest that liver plasma membranes from obese Zucker rats express an inactive Gi alpha subunit. Thus lesions in liver Gi functioning are seen in insulin-resistant obese rats and in alloxan- and streptozotocin-induced diabetic rats which also show resistance as regards the acute actions of insulin. Liver plasma membranes of obese animals also showed an impairment in the coupling of glucagon receptors to Gs-controlled adenylate cyclase, with the Kd values for activation by glucagon being 17.3 and 126 nM for lean and obese animals respectively. Membranes from obese animals also showed a reduced ability for high concentration of p[NH]ppG to activate adenylate cyclase. The use of [32P]-NAD+ and thiol-preactivated cholera toxin to label the 43 kDa and 52 kDa forms of the alpha-subunit of Gs showed that a reduced labelling occurred using liver plasma membranes from obese animals. It is suggested that abnormalities in the levels of expression of primarily the 52 kDa form of alpha-Gs may give rise to the abnormal coupling between glucagon receptors and adenylate cyclase in liver membranes from obese (fa/fa) Zucker rats.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Houslay MD,Gawler DJ,Milligan G,Wilson Adoi
10.1016/0898-6568(89)90016-8subject
Has Abstractpub_date
1989-01-01 00:00:00pages
9-22issue
1eissn
0898-6568issn
1873-3913pii
0898-6568(89)90016-8journal_volume
1pub_type
杂志文章abstract::Although increasing evidence demonstrated that deregulation of mircoRNA-503 (miRNA-503) contributes to tumorigenesis, little is known about the biological role and intrinsic regulatory mechanisms of miR-503 in prostate cancer (PCa). In present study, we found that miR-503 was significantly downregulated in advanced PC...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2016.06.002
更新日期:2016-09-01 00:00:00
abstract::Measurements of prostaglandin E2 (PGE2)-induced adenylyl cyclase activity in membranes isolated from epididymal rat adipocytes revealed inhibition of cAMP production at low concentrations of PGE2 (less than 10 mM) and stimulation at higher concentrations. This biphasic effect of PGE2 was obtained when adenylyl cyclase...
journal_title:Cellular signalling
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doi:10.1016/0898-6568(92)90073-h
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(90)90032-6
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abstract::We report here a direct modulation by mast cell tryptase of endothelial barrier function through activation of proteinase-activated receptor-2 (PAR-2). In cultured bovine aortic endothelial cells (BAECs), tryptase, trypsin and PAR-2 activating peptide impaired the barrier function as determined by the permeability of ...
journal_title:Cellular signalling
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doi:10.1016/s0898-6568(03)00014-7
更新日期:2003-08-01 00:00:00
abstract::Signal transducer and activator of transcription 3 (Stat3) is a transcription factor that is involved in cell survival and proliferation and has been found to be persistently activated in most human cancers mainly through its phosphorylation at Tyr-705. However, the role and regulation of Stat3 Ser-727 phosphorylation...
journal_title:Cellular signalling
pub_type: 杂志文章
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abstract::The implication of protein kinase C in the phenomenon of pancreatic acinar cell desensitization to carbamylcholine, caerulein and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was investigated using a potent PKC inhibitor, staurosporine. At a concentration of 1 microM, staurosporine caused a maximum 64%...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(91)90018-p
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2006.02.010
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(97)00189-7
更新日期:1998-07-01 00:00:00
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journal_title:Cellular signalling
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doi:10.1016/j.cellsig.2014.10.009
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journal_title:Cellular signalling
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2007.02.009
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.07.005
更新日期:2010-11-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(99)00019-4
更新日期:1999-07-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2003.11.002
更新日期:2004-06-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.09.016
更新日期:2009-01-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.01.010
更新日期:2008-05-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2005.04.003
更新日期:2005-09-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(93)90026-i
更新日期:1993-05-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2016.02.011
更新日期:2016-05-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章,评审
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.11.017
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(94)00082-m
更新日期:1995-03-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2016.08.018
更新日期:2016-12-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2020.109638
更新日期:2020-08-01 00:00:00
abstract::Agonist stimulation of G-protein coupled receptors (GPCRs) results in the redistribution of the receptor from the cell surface into intracellular compartments through the process of endocytosis. Monitoring ligand-mediated internalization of GPCRs in living cells has become experimentally accessible by applying fluores...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.05.017
更新日期:2008-10-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(98)00052-7
更新日期:1999-03-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2019.109361
更新日期:2019-11-01 00:00:00
abstract::Bone Morphogenetic Proteins (BMPs) are potent growth factors belonging to the Transforming Growth Factor Beta superfamily. To date over 20 members have been identified in humans with varying functions during processes such as embryogenesis, skeletal formation, hematopoiesis and neurogenesis. Though their functions hav...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2010.10.003
更新日期:2011-04-01 00:00:00
abstract::MAP Kinase Phosphatase-2 (MKP-2) is a dual specific nuclear phosphatase which is selective for both ERK and JNK, MAP kinases implicated in the regulation of apoptosis in response to genotoxic stress. Here we report the conditional expression of MKP-2 in human embryonic kidney cells 293. We demonstrate that Flag-WT-MKP...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2005.01.003
更新日期:2005-10-01 00:00:00